Cyclooxygenase-2 (COX-2) is antiapoptotic and is implicated in tumorigenesis. Recent reports, however, have also ascribed a proapoptotic action to inducible COX-2. We show here for the first time that a stilbene, resveratrol, induces nuclear accumulation of COX-2 protein in human breast cancer MCF-7 and MDA-MB-231 cell cultures. The induction of COX-2 accumulation by resveratrol is mitogen-activated protein kinase (MAPK; extracellular signal -regulated kinase 1/2)- and activator protein 1-dependent. Nuclear COX-2 in resveratrol-treated cells colocalizes with Ser 15-phosphorylated p53 and with p300, a coactivator for p53-dependent gene expression. The interaction of COX-2, p53, and p300, as well as resveratrol-induced apoptosis, was inhibited by a MAPK activation inhibitor, PD98059. A specific inhibitor of COX-2, NS398, and small interfering RNA knockdown of COX-2 were associated with reduced p53 phosphorylation and consequent decrease in p53-dependent apoptosis in resveratrol-treated cells. We conclude that nuclear accumulation of COX-2 can be induced by resveratrol and that the COX has a novel intranuclear colocalization with Ser 15-phosphorylated p53 and p300, which facilitates apoptosis in resveratrol-treated breast cancer cell.
ASJC Scopus subject areas
- Drug Discovery
Tang, H. Y., Shih, A., Cao, H. J., Davis, F. B., Davis, P. J., & Lin, H. Y. (2006). Resveratrol-induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cells. Molecular Cancer Therapeutics, 5(8), 2034-2042. https://doi.org/10.1158/1535-7163.MCT-06-0216